Obesity-induced and Weight-loss-induced Physiological Factors Affecting Weight Regain

Overview

Journal Nat Rev Endocrinol

Specialty Endocrinology

Date 2023 Sep 11

PMID 37696920

Authors

Marleen A van Baak

Edwin C M Mariman

Affiliations

Soon will be listed here.

Abstract

Weight regain after successful weight loss resulting from lifestyle interventions is a major challenge in the management of overweight and obesity. Knowledge of the causal mechanisms for weight regain can help researchers and clinicians to find effective strategies to tackle weight regain and reduce obesity-associated metabolic and cardiovascular complications. This Review summarizes the current understanding of a number of potential physiological mechanisms underlying weight regain after weight loss, including: the role of adipose tissue immune cells; hormonal and neuronal factors affecting hunger, satiety and reward; resting energy expenditure and adaptive thermogenesis; and lipid metabolism (lipolysis and lipid oxidation). We describe and discuss obesity-associated changes in these mechanisms, their persistence during weight loss and weight regain and their association with weight regain. Interventions to prevent or limit weight regain based on these factors, such as diet, exercise, pharmacotherapy and biomedical strategies, and current knowledge on the effectiveness of these interventions are also reviewed.

Citing Articles

Intentional Weight Loss, Waist Circumference Reduction, and Mortality Risk Among Postmenopausal Women.

Hendryx M, Manson J, Ostfeld R, Chlebowski R, LeBlanc E, Waring M JAMA Netw Open. 2025; 8(3):e250609.

PMID: 40048162 PMC: 11886725. DOI: 10.1001/jamanetworkopen.2025.0609.

GPCRs in hypothalamic neurons and their roles in controlling food intake and metabolism.

Qiu T, Fu O Front Mol Neurosci. 2025; 18:1536577.

PMID: 39974186 PMC: 11835808. DOI: 10.3389/fnmol.2025.1536577.

The impact of intermittent energy restriction on women's health.

Harvie M, Haiba M Proc Nutr Soc. 2025; :1-27.

PMID: 39931753 PMC: 7617461. DOI: 10.1017/S0029665125000059.

Revisiting the role of IL-27 in obesity-related metabolic diseases: safeguard or perturbation?.

An J, Fu D, Chen X, Guan C, Li L, Bai J Front Immunol. 2025; 15:1498288.

PMID: 39906735 PMC: 11792170. DOI: 10.3389/fimmu.2024.1498288.

The Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation for the Management of Obesity and Non-Alcoholic Fatty Liver Disease: Recent Updates.

Yan R, Cao Y Biomedicines. 2025; 13(1).

PMID: 39857788 PMC: 11762999. DOI: 10.3390/biomedicines13010206.

References

van Baak M, Mariman E . Mechanisms of weight regain after weight loss - the role of adipose tissue. Nat Rev Endocrinol. 2019; 15(5):274-287. DOI: 10.1038/s41574-018-0148-4. View

Berthoud H, Seeley R, Roberts S . Physiology of Energy Intake in the Weight-Reduced State. Obesity (Silver Spring). 2021; 29 Suppl 1:S25-S30. DOI: 10.1002/oby.23080. View

Hill D, Lim H, Kim Y, Ho W, Foong Y, Nelson V . Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue. Proc Natl Acad Sci U S A. 2018; 115(22):E5096-E5105. PMC: 5984532. DOI: 10.1073/pnas.1802611115. View

Hildreth A, Ma F, Wong Y, Sun R, Pellegrini M, OSullivan T . Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat Immunol. 2021; 22(5):639-653. PMC: 8102391. DOI: 10.1038/s41590-021-00922-4. View

Weisberg S, McCann D, Desai M, Rosenbaum M, Leibel R, Ferrante Jr A . Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003; 112(12):1796-808. PMC: 296995. DOI: 10.1172/JCI19246. View

Xu H, Barnes G, Yang Q, Tan G, Yang D, Chou C . Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003; 112(12):1821-30. PMC: 296998. DOI: 10.1172/JCI19451. View

Lumeng C, Bodzin J, Saltiel A . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007; 117(1):175-84. PMC: 1716210. DOI: 10.1172/JCI29881. View

Caslin H, Bhanot M, Bolus W, Hasty A . Adipose tissue macrophages: Unique polarization and bioenergetics in obesity. Immunol Rev. 2020; 295(1):101-113. PMC: 8015437. DOI: 10.1111/imr.12853. View

Cottam M, Caslin H, Winn N, Hasty A . Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice. Nat Commun. 2022; 13(1):2950. PMC: 9135744. DOI: 10.1038/s41467-022-30646-4. View

10.

Clement K, Viguerie N, Poitou C, Carette C, Pelloux V, Curat C . Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J. 2004; 18(14):1657-69. DOI: 10.1096/fj.04-2204com. View

11.

Capel F, Klimcakova E, Viguerie N, Roussel B, Vitkova M, Kovacikova M . Macrophages and adipocytes in human obesity: adipose tissue gene expression and insulin sensitivity during calorie restriction and weight stabilization. Diabetes. 2009; 58(7):1558-67. PMC: 2699855. DOI: 10.2337/db09-0033. View

12.

Caslin H, Cottam M, Pinon J, Boney L, Hasty A . Weight cycling induces innate immune memory in adipose tissue macrophages. Front Immunol. 2023; 13:984859. PMC: 9876596. DOI: 10.3389/fimmu.2022.984859. View

13.

Schmitz J, Evers N, Awazawa M, Nicholls H, Bronneke H, Dietrich A . Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss. Mol Metab. 2016; 5(5):328-339. PMC: 4837291. DOI: 10.1016/j.molmet.2015.12.001. View

14.

Liu P, Wang H, Li X, Chao T, Teav T, Christen S . α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol. 2017; 18(9):985-994. DOI: 10.1038/ni.3796. View

15.

Chavakis T, Alexaki V, Ferrante Jr A . Macrophage function in adipose tissue homeostasis and metabolic inflammation. Nat Immunol. 2023; 24(5):757-766. DOI: 10.1038/s41590-023-01479-0. View

16.

Netea M, Dominguez-Andres J, Barreiro L, Chavakis T, Divangahi M, Fuchs E . Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020; 20(6):375-388. PMC: 7186935. DOI: 10.1038/s41577-020-0285-6. View

17.

Cao Y, Dong Q, Wang D, Liu Y, Zhang P, Yu X . TIDB: a comprehensive database of trained immunity. Database (Oxford). 2021; 2021. PMC: 8271126. DOI: 10.1093/database/baab041. View

18.

Yi J, Cox M, Zajac A . T-cell exhaustion: characteristics, causes and conversion. Immunology. 2010; 129(4):474-81. PMC: 2842494. DOI: 10.1111/j.1365-2567.2010.03255.x. View

19.

Porsche C, Delproposto J, Geletka L, ORourke R, Lumeng C . Obesity results in adipose tissue T cell exhaustion. JCI Insight. 2021; 6(8). PMC: 8119198. DOI: 10.1172/jci.insight.139793. View

20.

Varghese M, Griffin C, McKernan K, Eter L, Lanzetta N, Agarwal D . Sex Differences in Inflammatory Responses to Adipose Tissue Lipolysis in Diet-Induced Obesity. Endocrinology. 2018; 160(2):293-312. PMC: 6330175. DOI: 10.1210/en.2018-00797. View